Microglial cells are the resident innate immune cell in the brain and exhibit a range of distinct morphologies and distribution during gestation. Studies in the past decade have shown that microglia regulate key processes in the developing brain including synapse development, axonal path finding, and cortical layer formation. We recently showed that microglia regulate cell production in the prenatal cerebral cortex through phagocytosis of neural precursor cells (NPCs), but the full range of functions performed by fetal microglial cells are not well understood. We have discovered a novel population of periventricular microglia that make extensive contact with NPCs undergoing division at the ventricular lumen in the fetal rhesus monkey telencephalon. The studies proposed in this application are designed to address significant gaps in our knowledge on the function of fetal microglial cells during critical windows of nonhuman primate brain development. This proposal will generate new insights into normal development that are critical to our understanding of ontogeny through the following Specific Aims: (1) Define the role of fetal periventricular microglia in NPC detachment through live time-lapse videomicroscopy in cultured explants; and (2) Determine the role of purinergic signaling in regulating periventricular microglia contact with NPCs and NPC detachment in the fetal monkey telencephalon. The proposed studies will enhance our understanding of factors that regulate development of the cerebral cortex and further define the impact microglial cell function has on the developing fetal brain.